Cannabidiol Affects Extracellular Vesicle Release, miR21 and miR126, and Reduces Prohibitin Protein in Glioblastoma Multiforme Cells

Uchini S Kosgodage, Pinar Uysal-Onganer, Amy MacLatchy, Rhys Mould, Alistair Nunn, Geoffrey Guy, Igor Kraev, Nicholas Chatterton, Jameel Inal, E. Louise Thomas, Jimmy Bell, Sigrun Lange

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)
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Abstract

Glioblastoma multiforme (GBM) is the most common and aggressive form of primary malignant brain tumor in adults, with poor prognosis. Extracellular vesicles (EVs) are key-mediators for cellular communication through transfer of proteins and genetic material. Cancers, such as GBM, use EV release for drug-efflux, pro-oncogenic signaling, invasion and immunosuppression; thus the modulation of EV release and cargo is of considerable clinical relevance. As EV-inhibitors have been shown to increase sensitivity of cancer cells to chemotherapy, and we recently showed that cannabidiol (CBD) is such an EV-modulator, we investigated whether CBD affects EV profile in GBM cells in the presence and absence of temozolomide (TMZ). Compared to controls, CBD-treated cells released EVs containing lower levels of pro-oncogenic miR21 and increased levels of anti-oncogenic miR126; these effects were greater than with TMZ alone. In addition, prohibitin (PHB), a multifunctional protein with mitochondrial protective properties and chemoresistant functions, was reduced in GBM cells following 1 h CBD treatment. This data suggests that CBD may, via modulation of EVs and PHB, act as an adjunct to enhance treatment efficacy in GBM, supporting evidence for efficacy of cannabinoids in GBM.
Original languageEnglish
Pages (from-to)513-522
Number of pages10
JournalTranslational Oncology
Volume12
Issue number3
Early online date28 Dec 2018
DOIs
Publication statusPublished - 1 Mar 2019

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